Pathologic Response to Primary Systemic Therapy With FOLFIRINOX in Patients With Resectable Pancreatic Cancer.

BACKGROUND: Primary systemic therapy in resectable pancreatic cancer is currently under investigation. FOLFIRINOX has been shown to be effective in both the adjuvant and metastatic settings and is increasingly being used on and off study in the neoadjuvant setting. The objective pathologic response elicited by this regimen in truly resectable disease has not as yet been widely reported. METHODS: This analysis focuses on 14 patients with resectable pancreatic cancer who were treated in a pilot study of primary systemic therapy, using 4 cycles of neoadjuvant FOLFIRINOX before surgery. A dedicated pancreatic pathologist reviewed all of the subsequent surgical specimens to assess the degree of tumor regression elicited by this approach, according to the scoring system proposed by Evans. RESULTS: Four patients (28.6%) had Evans grade I, 4 (28.6%) Evans grade IIa, 2 (14.2%) Evans grade IIb, and 4 (28.6%) Evans grade III response to the primary systemic therapy. There were no Evans grade IV responses. CONCLUSIONS: The results are intriguing with 28% of the specimens showing destruction of <10% of tumor cells, and only 28% achieving >90% destruction of tumor cells. The significant variation in response once again confirms the known heterogeneity in the biology of this cancer and clearly FOLFIRINOX is not equally effective in all patients. Future studies evaluating primary systemic therapy in pancreatic cancer should examine the optimal duration of therapy before surgery and should include a standardized pathologic grading scheme to better enable comparison of results.

Predicting malaria cases using remotely sensed environmental variables in Nkomazi, South Africa.

There has been a conspicuous increase in malaria cases since 2016/2017 over the three malaria-endemic provinces of South Africa. This increase has been linked to climatic and environmental factors. In the absence of adequate traditional environmental/climatic data covering ideal spatial and temporal extent for a reliable warning system, remotely sensed data are useful for the investigation of the relationship with, and the prediction of, malaria cases. Monthly environmental variables such as the normalised difference vegetation index (NDVI), the enhanced vegetation index (EVI), the normalised difference water index (NDWI), the land surface temperature for night (LSTN) and day (LSTD), and rainfall were derived and evaluated using seasonal autoregressive integrated moving average (SARIMA) models with different lag periods. Predictions were made for the last 56 months of the time series and were compared to the observed malaria cases from January 2013 to August 2017. All these factors were found to be statistically significant in predicting malaria transmission at a 2-months lag period except for LSTD which impact the number of malaria cases negatively. Rainfall showed the highest association at the two-month lag time (r=0.74; P<0.001), followed by EVI (r=0.69; P<0.001), NDVI (r=0.65; P<0.001), NDWI (r=0.63; P<0.001) and LSTN (r=0.60; P<0.001). SARIMA without environmental variables had an adjusted R2 of 0.41, while SARIMA with total monthly rainfall, EVI, NDVI, NDWI and LSTN were able to explain about 65% of the variation in malaria cases. The prediction indicated a general increase in malaria cases, predicting about 711 against 648 observed malaria cases. The development of a predictive early warning system is imperative for effective malaria control, prevention of outbreaks and its subsequent elimination in the region.

DEHP exposure destroys blood-testis barrier (BTB) integrity of immature testes through excessive ROS-mediated autophagy.

Di-(2-ethylhexyl) phthalate (DEHP), is known to impair testicular functions and reproduction. However, its effects on immature testis Blood-testis barrier (BTB) and the underlying mechanisms remain obscure. We constructed a rat model to investigate the roles of autophagy in BTB toxicity induced by DEHP. Sprague-Dawley rats were developmentally exposed to 0, 250 and 500 mg/kg DEHP via intragastric administration from postnatal day (PND) 1 to PND 35. Testicular morphology, expressions of BTB junction proteins and autophagy related proteins were detected. In addition, expressions of oxidative stress markers were also analyzed. Our results demonstrated that developmental DEHP exposure induced decreasing organ coefficients of immature testes and severe testicular damage in histomorphology. The expressions of junctional proteins were down-regulated significantly after DEHP treatment. Intriguingly, DEHP simultaneously increased the number of autophagosomes and the levels of autophagy marker LC3-II and p62, suggesting that the accumulated autophagosomes resulted from impaired autophagy degradation. Moreover, the expressions of HO-1 and SOD levels remarkably decreased after DEHP exposure. Vitamins E and C could alleviate the DEHP-induced oxidative stress, reverse the autophagy defect and restore the BTB impairment. Taken together, DEHP exposure destroys immature testis blood-testis barrier (BTB) integrity through excessive ROS-mediated autophagy.

Identification and comprehensive evaluation of a novel biocontrol agent Bacillus atrophaeus JZB120050.

Bacillus spp. have long been used as biocontrol agents because of their efficient broad-spectrum antimicrobial activity. We identified a novel strain of Bacillus atrophaeus, named JZB120050, from soil. B. atrophaeus JZB120050 had a strong inhibitory effect against Botrytis cinerea and many other phytopathogens. Gas chromatography-mass spectrometry showed that B. atrophaeus JZB120050 produced many secondary metabolites, such as alkanes, alkenes and acids; some of which were related to pathogen inhibition. Enzyme activity analysis showed that B. atrophaeus JZB120050 secreted cell-wall-degrading enzymes, including chitinase, glucanase and protease, which degraded fungal cell walls. Both the novel glucanase gene bglu and chitinase gene chit1 were cloned and heterologously expressed in Escherichia coli and the products showed strong enzyme activity. In addition, B. atrophaeus JZB120050 secreted siderophores and formed a significant biofilm. Future studies should focus on these antimicrobial factors to facilitate widespread application in the field of agricultural biocontrol.

Primary systemic therapy in resectable pancreatic ductal adenocarcinoma using mFOLFIRINOX: A pilot study.

BACKGROUND AND OBJECTIVES: Surgery followed by gemcitabine and/or a fluoropyrimidine is standard therapy for resectable PDAC. mFOLFIRINOX (oxaliplatin 85 mg/m2 , irinotecan 180 mg/m2 , leucovorin 400 mg/m2 Day 1, 5-FU 2400 mg/m2 × 48 h IV, peg-filgrastim 6 mg SQ day 3, every 14 days) has substantial activity in metastatic PDAC. We wished to determine the tolerability/efficacy of peri-operative mFOLFIRINOX in resectable PDAC. METHODS: Patients with resectable PDAC (ECOG PS 0/1) received four cycles of mFOLFIRINOX pre- and post-surgery. The primary endpoint was completion of preoperative chemotherapy plus resection. Secondary endpoints included completion of all therapy, R0 resection, treatment related toxicity, PFS, and OS. RESULTS: Twenty-one patients enrolled: median age 62 (47-78); 20/21 (95%) completed four cycles of preoperative mFOLFIRINOX; response by RECIST was 1 CR, 3 PR, 16 SD; 17/21 (81%) completed resection, 16/21 (76%) R0; 14/21 (66%) completed four cycles of postoperative mFOLFIRINOX. Grade 3 and 4 toxicity occurred in 23% and 14% patients pre-operatively, 26% and 6.0% post-operatively. Nine patients are alive with median follow-up of 27.7 (3.1-47.1) months. CONCLUSIONS: PST using mFOLFIRINOX in resectable PDAC is feasible and tolerable. R0 resection rate is high and survival promising, requiring longer follow-up and larger studies for definitive assessment.

Identification of genes and proteins associated with anagen wool growth.

Identifying genes of major effect for wool growth would offer strategies for improving the quality and increasing the yield of fine wool. In this study, we employed the Agilent Sheep Gene Expression Microarray and proteomic technology to investigate the gene expression patterns of body side skin (more wool growing) in Aohan fine wool sheep (a Chinese indigenous breed) in comparison with groin skin (no wool growing) at the anagen stage of the wool follicle. A microarray study revealed that 4772 probes were differentially expressed, including 2071 upregulated and 2701 downregulated probes, in the comparisons of body side skin vs. groin skin (S/G). The microarray results were verified by means of quantitative PCR. A total of 1099 probes were assigned to unique genes/transcripts. The number of distinct genes/transcripts (annotated) was 926, of which 352 were upregulated and 574 were downregulated. In S/G, 13 genes were upregulated by more than 10 fold, whereas 60 genes were downregulated by more than 10 fold. Further analysis revealed that the majority of the genes possibly related to the wool growth could be assigned to categories including regulation of cell division, intermediate filament, cytoskeletal part and growth factor activity. Several potential gene families may participate in hair growth regulation, including fibroblast growth factors, transforming growth factor-ß, WNTs, insulin-like growth factor, vascular endothelial growth factors and so on. Proteomic analysis also revealed 196 differentially expressed protein points, of which 121 were identified as single protein points.

Preoperative Modified FOLFIRINOX Treatment Followed by Capecitabine-Based Chemoradiation for Borderline Resectable Pancreatic Cancer: Alliance for Clinical Trials in Oncology Trial A021101.

IMPORTANCE: Although consensus statements support the preoperative treatment of borderline resectable pancreatic cancer, no prospective, quality-controlled, multicenter studies of this strategy have been conducted. Existing studies are retrospective and confounded by heterogeneity in patients studied, therapeutic algorithms used, and outcomes reported. OBJECTIVE: To determine the feasibility of conducting studies of multimodality therapy for borderline resectable pancreatic cancer in the cooperative group setting. DESIGN, SETTING, AND PARTICIPANTS: A prospective, multicenter, single-arm trial of a multimodality treatment regimen administered within a study framework using centralized quality control with the cooperation of 14 member institutions of the National Clinical Trials Network. Twenty-nine patients with biopsy-confirmed pancreatic cancer preregistered, and 23 patients with tumors who met centrally reviewed radiographic criteria registered. Twenty-two patients initiated therapy (median age, 64 years [range, 50-76 years]; 55% female). Patients registered between May 29, 2013, and February 7, 2014. INTERVENTIONS: Patients received modified FOLFIRINOX treatment (85 mg/m2 of oxaliplatin, 180 mg/m2 of irinotecan hydrochloride, 400 mg/m2 of leucovorin calcium, and then 2400 mg/m2 of 5-fluorouracil for 4 cycles) followed by 5.5 weeks of external-beam radiation (50.4 Gy delivered in 28 daily fractions) with capecitabine (825 mg/m2 orally twice daily) prior to pancreatectomy. MAIN OUTCOMES AND MEASURES: Feasibility, defined by the accrual rate, the safety of the preoperative regimen, and the pancreatectomy rate. RESULTS: The accrual rate of 2.6 patients per month was superior to the anticipated rate. Although 14 of the 22 patients (64% [95% CI, 41%-83%]) had grade 3 or higher adverse events, 15 of the 22 patients (68% [95% CI, 49%-88%]) underwent pancreatectomy. Of these 15 patients, 12 (80%) required vascular resection, 14 (93%) had microscopically negative margins, 5 (33%) had specimens that had less than 5% residual cancer cells, and 2 (13%) had specimens that had pathologic complete responses. The median overall survival of all patients was 21.7 months (95% CI, 15.7 to not reached) from registration. CONCLUSIONS AND RELEVANCE: The successful completion of this collaborative study demonstrates the feasibility of conducting quality-controlled trials for this disease stage in the multi-institutional setting. The data generated by this study and the logistical elements that facilitated the trial's completion are currently being used to develop cooperative group trials with the goal of improving outcomes for this subset of patients. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT01821612.

Increased expression of long noncoding RNA TUG1 predicts a poor prognosis of gastric cancer and regulates cell proliferation by epigenetically silencing of p57.

Recent evidence highlights long noncoding RNAs (lncRNAs) as crucial regulators of cancer biology that contribute to tumorigenesis. LncRNA TUG1 was initially detected in a genomic screen for genes upregulated in response to taurine treatment in developing mouse retinal cells. Our previous study showed that TUG1 could affect cell proliferation through epigenetically regulating HOXB7 in human non-small cell lung cancer. However, the clinical significance and potential role of TUG1 in GC remains unclear. In this study, we found that TUG1 is significantly increased and is correlated with outcomes in gastric cancer (GC). Further experiments revealed that knockdown of TUG1 repressed GC proliferation both in vitro and in vivo. Mechanistic investigations showed that TUG1 has a key role in G0/G1 arrest. We further demonstrated that TUG1 was associated with PRC2 and that this association was required for epigenetic repression of cyclin-dependent protein kinase inhibitors, including p15, p16, p21, p27 and p57, thus contributing to the regulation of GC cell cycle and proliferation. Together, our results suggest that TUG1, as a regulator of proliferation, may serve as a candidate prognostic biomarker and target for new therapies in human GC.

Environmental factors and population at risk of malaria in Nkomazi municipality, South Africa.

OBJECTIVE: Nkomazi local municipality of South Africa is a high-risk malaria region with an incidence rate of about 500 cases per 100 000. We examined the influence of environmental factors on population (age group) at risk of malaria. METHODS: r software was used to statistically analyse data. Using remote sensing technology, a Landsat 8 image of 4th October 2015 was classified using object-based classification and a 5-m resolution. Spot height data were used to generate a digital elevation model of the area. RESULTS: A total of 60 718 malaria cases were notified across 48 health facilities in Nkomazi municipality between January 1997 and August 2015. Malaria incidence was highly associated with irrigated land (P = 0.001), water body (P = 0.011) and altitude ≤400 m (P = 0.001). The multivariate model showed that with 10% increase in the extent of irrigated areas, malaria risk increased by almost 39% in the entire study area and by almost 44% in the 2-km buffer zone of selected villages. Malaria incidence is more pronounced in the economically active population aged 15-64 and in males. Both incidence and case fatality rate drastically declined over the study period. CONCLUSION: A predictive model based on environmental factors would be useful in the effort towards malaria elimination by fostering appropriate targeting of control measures and allocating of resources.

LincHOTAIR epigenetically silences miR34a by binding to PRC2 to promote the epithelial-to-mesenchymal transition in human gastric cancer.

lncRNAs play important roles in the epigenetic regulation of carcinogenesis and progression. Previous studies suggest that HOTAIR contributes to gastric cancer (GC) development, and the overexpression of HOTAIR predicts a poor prognosis. In this study, we found that HOTAIR was more highly expressed in diffuse-type GC than in intestinal type (P=0.048). In the diffuse type, there is significant relationship between HOTAIR expression and DFS (P<0.001). CDH1 was downregulated in diffuse-type GC tissues (P=0.0007) and showed a negative relationship with HOTAIR (r(2)=0.154, P=0.0354). In addition, HOTAIR knockdown significantly repressed migration, invasion and metastasis both in vitro and vivo and reversed the epithelial-to-mesenchymal transition in GC cells. We also showed that HOTAIR recruiting and binding to PRC2 epigenetically represses miR34a, which controls the targets C-Met (HGF/C-Met/Snail pathway) and Snail, thus contributing to GC cell-EMT process and accelerating tumor metastasis. Moreover, it is demonstrated that HOTAIR crosstalk with microRNAs during epigenetic regulation. Our results suggest that HOTAIR acts as an EMT regulator and may be a candidate prognostic biomarker and a target for new therapies in GC patients.

Pancreatic cancer and FOLFIRINOX: a new era and new questions.

FOLFIRINOX (FFX) was introduced to clinical practice in 2010 following publication of the PRODIGE 4/ACCORD 11 study, which compared this novel regimen to gemcitabine in metastatic pancreatic cancer. Median overall survival, progression-free survival, and objective responses were all superior with FFX and there was improved time to definitive deterioration in quality of life. Despite initial concerns over toxicity, there has been rapid uptake of this regimen, both revolutionizing management and opening the door to innovative research. As experience with FFX has accrued, many questions have arisen including the management of toxicities, the impact of frequent modifications, the optimal number of cycles, integration with other regimens and modalities, interpretation of radiologic and serologic response, utility of molecular signatures, and potential benefit in unique clinical settings such as pre- and postsurgery. This review will closely examine these issues, not only to summarize current knowledge but also to fuel scientific debate.

Low expression of long noncoding RNA PANDAR predicts a poor prognosis of non-small cell lung cancer and affects cell apoptosis by regulating Bcl-2.

Recently, a novel class of transcripts, long noncoding RNAs (lncRNAs), is involved in diseases including cancer. Here, we investigated the the role of lncRNA PANDAR in the progression of non-small cell lung carcinoma (NSCLC). PANDAR, interacting with NF-YA, was generally downregulated in NSCLC tissues. In a cohort of 140 NSCLC patients, decreased PANDAR expression was negatively correlated with greater tumor size (P<0.001) and advanced TNM stage (P=0.002). Moreover, PANDAR could serve as an independent predictor for overall survival in NSCLC (P=0.015). Further experiments demonstrated that PANDAR expression was induced by p53, and chromatin immunoprecipitation (ChIP) assays confirmed that PANDAR was a direct transcriptional target of p53 in NSCLC cells. PANDAR overexpression significantly repressed the proliferation in vitro and in vivo. We also showed that PANDAR-mediated growth regulation is in part due to the transcriptional modulation of Bcl-2 by interacting with NF-YA, thus affecting NSCLC cell apoptosis. To our knowledge, this is the first report which showed the role of PANDAR in the progression of NSCLC. The p53/PANDAR/NF-YA/Bcl-2 interaction might serve as targets for NSCLC diagnosis and therapy.

EZH2-mediated epigenetic suppression of long noncoding RNA SPRY4-IT1 promotes NSCLC cell proliferation and metastasis by affecting the epithelial-mesenchymal transition.

Recent evidence indicates that long noncoding RNAs (lncRNAs) have a critical role in the regulation of cellular processes such as differentiation, proliferation, and metastasis. These lncRNAs are dysregulated in a variety of cancers and many function as tumor suppressors; however, the regulatory factors involved in silencing lncRNA transcription are poorly understood. In this study, we showed that epigenetic silencing of lncRNA SPRY4 intronic transcript 1 (SPRY4-IT1) occurs in non-small-cell lung cancer (NSCLC) cells through direct transcriptional repression mediated by the Polycomb group protein enhancer of zeste homolog 2 (EZH2). SPRY4-IT1 is derived from an intron within SPRY4, and is upregulated in melanoma cells; knockdown of its expression leads to cell growth arrest, invasion inhibition, and elevated rates of apoptosis. Upon depletion of EZH2 by RNA interference, SPRY4-IT1 expression was restored, and transfection of SPRY4-IT1 into NSCLC cells resulted in a significant antitumoral effect, both in culture and in xenografted nude mice. Moreover, overexpression of SPRY4-IT1 was found to have a key role in the epithelial-mesenchymal transition through the regulation of E-cadherin and vimentin expression. In EZH2-knockdown cells, which characteristically showed impaired cell proliferation and metastasis, the induction of SPRY4-IT1 depletion partially rescued the oncogenic phenotype, suggesting that SPRY4-IT1 repression has an important role in EZH2 oncogenesis. Of most relevance, translation of these findings into human NSCLC tissue samples demonstrated that patients with low levels of SPRY4-IT1 expression had a shorter overall survival time, suggesting that SPRY4-IT1 could be a biomarker for poor prognosis of NSCLC.

P53-regulated long non-coding RNA TUG1 affects cell proliferation in human non-small cell lung cancer, partly through epigenetically regulating HOXB7 expression.

Recently, a novel class of transcripts, long non-coding RNAs (lncRNAs), is being identified at a rapid pace. These RNAs have critical roles in diverse biological processes, including tumorigenesis. Here we report that taurine-upregulated gene 1 (TUG1), a 7.1-kb lncRNA, recruiting and binding to polycomb repressive complex 2 (PRC2), is generally downregulated in non-small cell lung carcinoma (NSCLC) tissues. In a cohort of 192 NSCLC patients, the lower expression of TUG1 was associated with a higher TNM stage and tumor size, as well as poorer overall survival (P<0.001). Univariate and multivariate analyses revealed that TUG1 expression serves as an independent predictor for overall survival (P<0.001). Further experiments revealed that TUG1 expression was induced by p53, and luciferase and chromatin immunoprecipitation (ChIP) assays confirmed that TUG1 was a direct transcriptional target of p53. TUG1 knockdown significantly promoted the proliferation in vitro and in vivo. Moreover, the lncRNA-mediated regulation of the expression of HOX genes in tumorigenesis and development has been recently receiving increased attention. Interestingly, inhibition of TUG1 could upregulate homeobox B7 (HOXB7) expression; ChIP assays demonstrated that the promoter of HOXB7 locus was bound by EZH2 (enhancer of zeste homolog 2), a key component of PRC2, and was H3K27 trimethylated. This TUG1-mediated growth regulation is in part due to specific modulation of HOXB7, thus participating in AKT and MAPK pathways. Together, these results suggest that p53-regulated TUG1 is a growth regulator, which acts in part through control of HOXB7. The p53/TUG1/PRC2/HOXB7 interaction might serve as targets for NSCLC diagnosis and therapy.

MiR-101 regulates apoptosis of trophoblast HTR-8/SVneo cells by targeting endoplasmic reticulum (ER) protein 44 during preeclampsia.

To investigate a possible association between miR-101 and apoptosis of human trophoblast cells mediated by endoplasmic reticulum protein 44 (ERp44) in preeclampsia (PE), we explored the expression of miR-101 in PE placentas (n=30) compared with normotensive pregnant placentas (n=30) and the correlation between miR-101 and ERp44 was also analyzed. Furthermore, both the apoptotic rate of trophoblast cells and the ER stress-induced apoptotic proteins were assayed when the HTR-8/SVneo cells were treated with miR-101 mimics or inhibitors in vitro. We found a lower expression of miR-101 and an inverse correlation between miR-101 and ERp44 protein in PE placentas. Upregulation of miR-101 expression could inhibit trophoblast HTR-8/SVneo cell apoptosis and repress ER stress-induced apoptotic proteins by targeting ERp44 in vitro, whereas inhibition of miR-101 could induce HTR-8/SVneo cell apoptosis. Our findings indicated that overexpression of miR-101 could downregulate ERp44 and suppress apoptosis in trophoblast cells during PE. Therefore, loss of miR-101 expression could contribute to ER stress-induced trophoblast cell apoptosis by targeting ERp44.

CA 19-9 nonproduction is associated with poor survival after resection of pancreatic adenocarcinoma.

BACKGROUND: Carbohydrate antigen (CA) 19-9 is the most common serum biomarker used in pancreatic adenocarcinoma (PC). Elevated preoperative levels have been shown to correlate with more advanced stage, greater risk of unresectability, and overall worse survival. The prognostic value of CA 19-9 nonproduction, which is present in an estimated 5% to 15% of the population, is unclear. We sought to determine whether CA 19-9 nonproduction was associated with worse survival after PC resection. METHODS: We retrospectively reviewed our institution's prospective pancreatic database for all PC patients with documented preoperative CA 19-9 values who underwent resection with curative intent from March 1992 to August 2009. After excluding 10 perioperative deaths, 200 patients remained for analysis. RESULTS: Mean and median follow-up was 23.3 and 16.1 months, respectively. Median survival in months for patients with preoperative CA 19-9 levels in U/mL by category was as follows: normal (5.1 to 36.9): 32, nonproduction (≤ 5): 21, mildly elevated (37 to 99.9): 35, highly elevated (100+): 16. Factors significantly associated with worse overall survival were: nonwhite race, nonproduction or highly elevated preoperative CA 19-9 (≥ 100 U/mL), estimated blood loss ≥ 1 L, tumor size (≥ 2 cm), lymph node-positivity, and advanced (3/4) histologic grade. On multivariate analysis, only CA 19-9 nonproduction or highly elevated production, estimated blood loss ≥ 1 L, advanced histologic grade, and node positivity remained significant in the final model. CONCLUSIONS: CA 19-9 nonproduction is not associated with improved survival after pancreatic cancer resection, as has previously been asserted, when compared with patients with normal and elevated levels.

Assessment of chemical and mineralogical characteristics of airborne dust in the Sistan region, Iran.

Windblown transport and deposition of dust is widely recognized as an important physical and chemical concern to climate, human health and ecosystems. Sistan is a region located in southeast Iran with extensive wind erosion, severe desertification and intense dust storms, which cause adverse effects in regional air quality and human health. To mitigate the impact of these phenomena, it is vital to ascertain the physical and chemical characteristics of airborne and soil dust. This paper examines for the first time, the mineralogical and chemical properties of dust over Sistan by collecting aerosol samples at two stations established close to a dry-bed lake dust source region, from August 2009 to August 2010. Furthermore, soil samples were collected from topsoil (0-5 cm depth) at several locations in the dry-bed Hamoun lakes and downwind areas. These data were analyzed to investigate the chemical and mineralogical characteristics of dust, relevance of inferred sources and contributions to air pollution. X-ray Diffraction (XRD) analysis of airborne and soil dust samples shows that the dust mineralogy is dominated mainly by quartz (30-40%), calcite (18-23%), muscovite (10-17%), plagioclase (9-12%), chlorite (~6%) and enstatite (~3%), with minor components of dolomite, microcline, halite and gypsum. X-ray Fluorescence (XRF) analyses of all the samples indicate that the most important oxide compositions of the airborne and soil dust are SiO(2), CaO, Al(2)O(3), Na(2)O, MgO and Fe(2)O(3), exhibiting similar percentages for both stations and soil samples. Estimates of Enrichment Factors (EFs) for all studied elements show that all of them have very low EF values, suggesting natural origin from local materials. The results suggest that a common dust source region can be inferred, which is the eroded sedimentary environment in the extensive Hamoun dry lakes lying to the north of Sistan.

Comprehensive review of the diagnosis and treatment of biliary tract cancer 2012. Part II: multidisciplinary management.

Biliary tract cancers (gallbladder cancer, intra- and extra-hepatic cholangiocarcinoma and selected periampullary cancers) accounted for 12,760 new cases of cancer in the USA in 2010. These tumors have a dismal prognosis with most patients presenting with advanced disease. Early, accurate diagnosis is essential, both for potential cure where possible and for optimal palliative therapy in all others. This review examines the currently available and emerging technologies for diagnosis and treatment of this group of diseases.

Comprehensive review of the diagnosis and treatment of biliary tract cancer 2012. Part I: diagnosis-clinical staging and pathology.

Biliary tract cancers (gallbladder cancer, intra- and extra-hepatic cholangiocarcinoma, and selected periampullary cancers) accounted for 12,760 new cases of cancer in the USA in 2010. These tumors have a dismal prognosis with most patients presenting with advanced disease. Early, accurate diagnosis is essential, both for potential cure where possible and for optimal palliative therapy in all others. This review examines the currently available and emerging technologies for diagnosis and treatment of this group of diseases.

Tumor necrosis factor (TNF)-α upregulates progesterone receptor-A by activating the NF-κB signaling pathway in human decidua after labor onset.

To date, the relationship between inflammatory cytokines and progesterone receptors (PRs) has been little studied, although both mediate the mechanism of parturition in human deciduas. Thus, the aim of study was to investigate the role of an inflammatory cytokine, tumor necrosis factor (TNF)-α, in regulating progesterone withdrawal in decidua at human parturition. TNF-α levels and PR isoforms were compared in intrauterine deciduas from women who were in labor (IL, n = 10) or who were not in labor (NIL, n = 10). Nuclear factor-kappaB (NF-κB) signaling and PR status were analyzed in NIL deciduas after TNF-α stimulation. Immunohistochemistry, western blotting, ELISA and reverse transcription-polymerase chain reaction (RT-PCR) were used to localize and quantitate protein and mRNA expression. TNF-α immunostaining, protein levels, PR-A/PR-B ratio and COX-2 level were significantly higher in IL deciduas (all P < 0.05). NF-κB was activated by TNF-α after 24 h stimulation in a dose-dependent manner, and was significantly inactivated by the NF-κB inhibitor panepoxydone, which was associated with decreased PR-A and COX-2 expression (P < 0.05) in not in labor deciduas. In conclusion, TNF-α may have an important role in regulating progesterone withdrawal in human decidua following labor onset.